Is COPG1 p.Leu830Pro (c.2489T>C) pathogenic?

COPG1 p.Leu830Pro (c.2489T>C) is classified Uncertain significance in COPG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: likely pathogenic (0.9976); Absent from gnomAD v4.1.

How common is COPG1 p.Leu830Pro (c.2489T>C) in the general population?

COPG1 p.Leu830Pro (c.2489T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPG1 p.Leu830Pro (c.2489T>C)?

AlphaMissense predicts likely pathogenic (score 0.9976) — an in-silico prediction, not a clinical call.

COPG1 p.Leu830Pro

c.2489T>C · rs2530390068 · VCV3076256

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9976 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9976	likely pathogenic · top 7% in COPG1
REVEL	0.646	pathogenic-leaning
SaProt	LLR -16.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.59, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 28 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COPG1
Protein: p.Leu830Pro
Coding: c.2489T>C
MANE Select: NM_016128
dbSNP: rs2530390068
Type: single nucleotide variant
Location: chr3:129275287 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.09 · 1 PDB
Residue 830: a β-strand; the 'interaction with znf289/arfgap2' region

Full COPG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPG1 p.Arg247His Uncertain significance ★★ ⚠ same type
COPG1 p.Leu864Met Uncertain significance ★★ ⚠ same type
COPG1 p.Thr64Met Uncertain significance ★★ ⚠ same type
COPG1 c.91-11T>C Benign ★★ same type
COPG1 c.939+13C>G Benign ★★ same type
COPG1 p.His221= Benign ★★ same type
COPG1 p.Ile92= Benign/Likely benign ★★ same type
COPG1 p.Leu240Val Benign/Likely benign ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/copg1-p-leu830pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown